Abstract
Introduction
MicroRNAs (miRNAs) are a class of small (19–25 nucleotides) noncoding RNAs that regulate the expressions of a wide variety of genes, including some involved in cancer development. Some recent studies show that DNA methylation contributes to down-regulation of microRNA-137 (miR-137) during tumorigenesis. Whether down-regulation of miR-137 also exists in gastric cancer is unknown.
Aim
Our aim was to test the hypothesis that down-regulation of miR-137 also exists in gastric cancer.
Methods
Expression of levels of miR-137 were examined using real-time PCR on paired gastric cancer and adjacent non-cancerous tissues. The methylation status is detected by MSP.
Results
Results show that miR-137 is downregulated by hypermethylation of the promoter in gastric cancer tissues. Epigenetic silencing of miR-137 induced an up-regulation of its targets, Cdc42. Restoration of the miR-137 expression in gastric cancer cell lines downregulated the Cdc42 expression. Restoration of the miR-137 and inactivation of Cdc42 induce apoptosis and cell cycle G1 arrest in gastric cancer cells. Furthermore, the miR-137 expression was found to be inversely correlated with CDC42 expression in gastric caner.
Conclusions
miR-137 is frequently down-regulated in gastric cancer and is a negative regulator of Cdc42.
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Qingjiang Chen and Xiaobing Chen contributed equally to this work.
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10620_2010_1536_MOESM1_ESM.jpg
MKN45 cells were subjected to Western blot analysis using antibodies against Cdc42, the phosphorylated form of ERK1/2, total ERK1/2 and Actin. Actin was used as an internal control. (JPEG 33 kb)
10620_2010_1536_MOESM2_ESM.jpg
The expression of Cdc-42 in gastric cancer cell lines MKN45 treated with or without demethylation agent DAC as determined by Western blot. Actin was used as an internal control. (JPEG 74 kb)
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Chen, Q., Chen, X., Zhang, M. et al. miR-137 Is Frequently Down-Regulated in Gastric Cancer and Is a Negative Regulator of Cdc42. Dig Dis Sci 56, 2009–2016 (2011). https://doi.org/10.1007/s10620-010-1536-3
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DOI: https://doi.org/10.1007/s10620-010-1536-3